Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes.

Autor: Skerget S; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Penaherrera D; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Chari A; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USA., Jagannath S; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USA., Siegel DS; Hackensack University Medical Center, Hackensack, NJ, USA., Vij R; Division of Oncology, Washington University, St. Louis, MO, USA., Orloff G; Virginia Cancer Specialists, Fairfax, VA, USA., Jakubowiak A; University of Chicago Medical Center, Chicago, IL, USA., Niesvizky R; Weill Cornell Medicine, New York City, NY, USA., Liles D; Division of Hematology/Oncology, East Carolina University, Greenville, NC, USA., Berdeja J; Sarah Cannon Research Institute, Nashville, TN, USA., Levy M; Baylor Scott and White Research Institute, Dallas, TX, USA., Wolf J; Department of Medicine, UCSF Medical Center, San Francisco, CA, USA., Usmani SZ; Levine Cancer Institute, Charlotte, NC, USA., Christofferson AW; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Nasser S; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Aldrich JL; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Legendre C; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Benard B; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Miller C; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Turner B; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Kurdoglu A; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Washington M; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Yellapantula V; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Adkins JR; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Cuyugan L; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Boateng M; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Helland A; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Kyman S; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., McDonald J; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Reiman R; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Stephenson K; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Tassone E; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Blanski A; Van Andel Institute, Grand Rapids, MI, USA., Livermore B; Van Andel Institute, Grand Rapids, MI, USA., Kirchhoff M; Van Andel Institute, Grand Rapids, MI, USA., Rohrer DC; Van Andel Institute, Grand Rapids, MI, USA., D'Agostino M; Division of Hematology, AOU Città della Salute e della Scienza di Torino, University of Torino and Department of Molecular Biotechnology and Health Sciences, Torino, Italy., Gamella M; Division of Hematology, AOU Città della Salute e della Scienza di Torino, University of Torino and Department of Molecular Biotechnology and Health Sciences, Torino, Italy., Collison K; Spectrum Health, Grand Rapids, MI, USA., Stumph J; Spectrum Health, Grand Rapids, MI, USA., Kidd P; Spectrum Health, Grand Rapids, MI, USA., Donnelly A; Precision for Medicine, Flemington, NJ, USA., Zaugg B; Precision for Medicine, Flemington, NJ, USA., Toone M; InStat Services, Chatham, NJ, USA., McBride K; InStat Services, Chatham, NJ, USA., DeRome M; Multiple Myeloma Research Foundation, Norwalk, CT, USA., Rogers J; Multiple Myeloma Research Foundation, Norwalk, CT, USA., Craig D; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Liang WS; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Gutierrez NC; Department of Hematology, University Hospital of Salamanca, IBSAL, Cancer Research Center-IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain., Jewell SD; Van Andel Institute, Grand Rapids, MI, USA., Carpten J; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA., Anderson KC; Dana-Farber Cancer Institute, Harvard Cancer Center, Boston, MA, USA., Cho HJ; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.; Multiple Myeloma Research Foundation, Norwalk, CT, USA., Auclair D; Multiple Myeloma Research Foundation, Norwalk, CT, USA., Lonial S; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA. sloni01@emory.edu., Keats JJ; Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA. jkeats@tgen.org.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2024 Sep; Vol. 56 (9), pp. 1878-1889. Date of Electronic Publication: 2024 Aug 19.
DOI: 10.1038/s41588-024-01853-0
Abstrakt: Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option.
(© 2024. The Author(s).)
Databáze: MEDLINE
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